281 results on '"Clifton O. Bingham"'
Search Results
2. Pain Sensitization as a Potential Mediator of the Relationship Between Sleep Disturbance and Subsequent Pain in Rheumatoid Arthritis
- Author
-
Jing Song, Lutfiyya N. Muhammad, Tuhina Neogi, Dorothy D. Dunlop, Alyssa Wohlfahrt, Marcy B. Bolster, Clifton O. Bingham, Daniel J. Clauw, Wendy Marder, and Yvonne C. Lee
- Subjects
Rheumatology - Abstract
Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain.We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors.Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect.Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA.
- Published
- 2022
3. Machine Learning Applied to <scp>Patient‐Reported</scp> Outcomes to Classify <scp>Physician‐Derived</scp> Measures of Rheumatoid Arthritis Disease Activity
- Author
-
Jeffrey R. Curtis, Yujie Su, Shawn Black, Stephen Xu, Wayne Langholff, Clifton O. Bingham, Shelly Kafka, and Fenglong Xie
- Subjects
Rheumatology - Abstract
Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated.Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data.A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%.ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are.
- Published
- 2022
4. Treatment goals for rheumatoid arthritis: patient engagement and goal collection
- Author
-
Zachary Predmore, Emily K Chen, Thomas W Concannon, Suzanne Schrandt, Susan J Bartlett, Clifton O Bingham, Richard Z Xie, Richard H Chapman, and Lori Frank
- Subjects
Health Policy - Abstract
Aim: We developed the Patient-Engaged Health Technology Assessment strategy for survey-based goal collection from patients to yield patient-important outcomes suitable for use in multi-criteria decision analysis. Methods: Rheumatoid arthritis patients were recruited from online patient networks for proof-of-concept testing of goal collection and prioritization using a survey. A Project Steering Committee and Expert Panel rated the feasibility of scaling to larger samples. Results: Survey respondents (n = 47) completed the goal collection exercise. Finding effective treatments was rated by respondents as the most important goal, and reducing stiffness was rated as the least important. Feedback from our steering committee and expert panel support the approach's feasibility for goal identification and ranking. Conclusion: Goals relevant for treatment evaluation can be identified and rated for importance by patients to permit wide input from patients with lived experience of disease.
- Published
- 2023
5. Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry
- Author
-
Anthony Sebba, Clifton O. Bingham, Vivian P. Bykerk, Stefano Fiore, Kerri Ford, Jud C. Janak, Dimitrios A. Pappas, Taylor Blachley, Swapna S. Dave, Joel M. Kremer, Miao Yu, and Ernest Choy
- Subjects
Rheumatology ,General Medicine - Abstract
Objective Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. Methods Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. Results Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). Conclusion This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population. Key Points• Patients with rheumatoid arthritis (RA) often require switching between biologics or targeted synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs) to achieve their treatment target.• Head-to-head randomized controlled trials (RCTs) in biologic-naïve RA patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy; however, there are no RCTs comparing these therapies in a population previously treated with b/tsDMARDs (i.e., b/ts-experienced patients).• This observational study compared the effectiveness of TNFi vs IL-6Ri (as mono- or combination therapy) in b/ts-experienced RA patients with moderate or high disease activity and found no significant differences in clinical outcomes for the two treatments.• A discrepancy is noted between our study and RCTs, which have shown superiority of IL-6Ri therapy (albeit in biologic-naïve patients). Further analyses may help elucidate the reason for this discrepancy in the real-world b/ts-experienced population.
- Published
- 2023
6. Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis
- Author
-
Ashley M. Curran, Alexander A. Girgis, Yura Jang, Jonathan D. Crawford, Mekha A. Thomas, Ryan Kawalerski, Jeff Coller, Clifton O. Bingham, Chan Hyun Na, and Erika Darrah
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized to drive the loss of immune tolerance to self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune responses to citrullinated self-antigens, in which arginine residues are converted to citrullines. Here, we investigate the hypothesis that citrullination exposes cryptic peptides by modifying protein structure and proteolytic cleavage. We show that citrullination alters processing and presentation of autoantigens, resulting in the generation of a unique citrullination-dependent repertoire composed primarily of native sequences. This repertoire stimulates T cells from RA patients with anti-citrullinated protein antibodies more robustly than controls. The generation of this unique repertoire is achieved through altered protease cleavage and protein destabilization, rather than direct presentation of citrulline-containing epitopes, suggesting a novel paradigm for the role of protein citrullination in the breach of immune tolerance in RA.
- Published
- 2023
7. PROMIS Provides a Broader Overview of Health-related Quality of Life Than the ESSPRI in Evaluation of Sjögren Syndrome
- Author
-
Dana D. DiRenzo, Susan Robinson, Clifton O. Bingham, Alan N. Baer, and Thomas Grader-Beck
- Subjects
Adult ,Cross-Sectional Studies ,Sjogren's Syndrome ,Rheumatology ,Immunology ,Quality of Life ,Humans ,Pain ,Immunology and Allergy ,Patient Reported Outcome Measures ,Article ,Fatigue ,Information Systems - Abstract
ObjectiveSjögren syndrome (SS) has a significant impact on health-related quality of life (HRQOL). We sought to evaluate how the Patient Reported Outcome Measurement Information System (PROMIS) domains in SS may supplement the European League Against Rheumatism (EULAR) Sjögren Syndrome Patient Reported Index (ESSPRI).MethodsA cross-sectional evaluation was performed on consecutive adult patients during visits to an SS clinic between March 2018 and February 2020. Each patient completed PROMIS short forms related to HRQOL and the ESSPRI, and had a clinical assessment. Patients were either classified as SS by 2016 American College of Rheumatology (ACR)/EULAR criteria, or as “sicca not otherwise specified (NOS)” and used as a comparison group. Univariable and multivariable linear regression models were used to evaluate predictors of PROMIS fatigue (-F), pain interference (-PI), and ability to participate in social roles and activities (-APS).ResultsTwo hundred twenty-seven patients with SS and 85 with sicca NOS were included and did not differ in ESSPRI domains; 26% of the SS and 20% of the sicca NOS group had concurrent autoimmune disease. In SS, PROMIS-PI, PROMIS-F, and PROMIS physical function were at least one-half SD worse than US population normative values. PROMIS-PI (r = 0.73) and PROMIS-F (r = 0.80) were highly correlated with ESSPRI pain and fatigue subdomains. Fatigue and pain interference, but not dryness or mood disturbance, were the strongest predictors of social participation in multivariable analysis.ConclusionIn our SS cohort, PROMIS instruments identified a high disease burden of pain interference, fatigue, and physical function. PROMIS-F strongly predicted PROMIS-APS. PROMIS-PI and PROMIS-F scores correlated highly with their respective ESSPRI domains. PROMIS instruments should be considered to identify relevant HRQOL patterns in SS.
- Published
- 2022
8. Maintenance of Patient-Reported Outcomes in Baricitinib-Treated Patients with Moderate-to-Severe Active Rheumatoid Arthritis: Post Hoc Analyses from Two Phase 3 Trials
- Author
-
Dalton, Sholter, Jianmin, Wu, Bochao, Jia, Hong, Zhang, Kirstin, Griffing, Julie, Birt, Paulo Jorge Simoes, Reis, Huaxiang, Liu, and Clifton O, Bingham
- Subjects
Rheumatology ,Immunology and Allergy - Abstract
Baricitinib has been shown to improve patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) who are inadequate responders (IR) to conventional synthetic and biologic disease-modifying antirheumatic drugs (csDMARDs and bDMARDs, respectively). We assessed the ability of baricitinib 2-mg to maintain minimal clinically important differences (MCIDs) in PROs until week 24 among week 4 and 12 responders.Data were from two phase 3 trials, RA-BUILD (NCT01721057; csDMARD-IR patients) and RA-BEACON (NCT01721044; bDMARD-IR patients). PROs included Pain Visual Analogue Scale, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, Short-Form 36 Physical Component Score, and Patient's Global Assessment of Disease Activity. Outcomes were evaluated by proportions of patients achieving MCID improvements, number needed to treat (NNT) at weeks 4, 12, and 24, proportions of patients maintaining MCID responses at week 24 among week 4 or 12 responders, and median time to achieve substantial response with baricitinib 2-mg versus placebo.A higher proportion of baricitinib-treated patients achieved MCID improvements, with NNTs ranging from 5 to 8 for baricitinib 2-mg versus placebo at week 24. Generally, early MCID responses in PROs at weeks 4 or 12 were better maintained through week 24 in RA patients treated with baricitinib 2-mg versus placebo. Patients treated with baricitinib 2-mg also achieved substantial PRO responses or normative values more quickly than placebo.These results suggest baricitinib-treated patients with RA achieving MCID improvement in PROs at weeks 4 and 12 maintained those improvements over time and that substantial PRO responses were achieved quickly.
- Published
- 2022
9. Predicting Disease Activity in Rheumatoid Arthritis with the Fibromyalgia Survey Questionnaire: Does the Severity of Fibromyalgia Symptoms Matter?
- Author
-
Alexander M. Gorzewski, Andrew C. Heisler, Tuhina Neogi, Lutfiyya N. Muhammad, Jing Song, Dorothy Dunlop, Clifton O. Bingham, Marcy B. Bolster, Daniel J. Clauw, Wendy Marder, and Yvonne C. Lee
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy - Abstract
ObjectiveTo determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD).MethodsOne hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables.ResultsIn multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04,P= 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08,P= 0.001), whereas the SSS was not (B = −0.03,P= 0.43).ConclusionHigher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ’s prediction of disease activity was the spatial extent of pain, as measured by the WPI.
- Published
- 2022
10. Fibromyalgianess and glucocorticoid persistence among patients with rheumatoid arthritis
- Author
-
Dorothy D. Dunlop, Yvonne C. Lee, Clifton O. Bingham, Beth I Wallace, Tuhina Neogi, Andrew C. Heisler, Meriah N Moore, Jing Song, Lutfiyya N. Muhammad, Daniel J. Clauw, Wendy Marder, Alyssa Wohlfahrt, and Marcy B. Bolster
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Fibromyalgia ,Logistic regression ,Arthritis, Rheumatoid ,Rheumatology ,Prednisone ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Glucocorticoids ,business.industry ,Odds ratio ,Clinical Science ,medicine.disease ,humanities ,Confidence interval ,Antirheumatic Agents ,Rheumatoid arthritis ,business ,Serostatus ,Glucocorticoid ,medicine.drug - Abstract
Objectives Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients. Methods We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ 10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP. Results Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]. Conclusion High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity.
- Published
- 2021
11. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases
- Author
-
Anne R. Bass, Eliza Chakravarty, Elie A. Akl, Clifton O. Bingham, Leonard Calabrese, Laura C. Cappelli, Sindhu R. Johnson, Lisa F. Imundo, Kevin L. Winthrop, Reuben J. Arasaratnam, Lindsey R. Baden, Roberta Berard, S. Louis Bridges, Jonathan T. L. Cheah, Jeffrey R. Curtis, Polly J. Ferguson, Ida Hakkarinen, Karen B. Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J. Smith, Jeffrey A. Sparks, Tiphanie P. Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S. Cunha, Joann Fontanarosa, Miriah C. Gillispie‐Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S. Lakin, Alexandra Legge, Mindy S. Lo, Megan M. Lockwood, Rebecca E. Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S. Turner, and James Reston
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy ,Article - Abstract
OBJECTIVE. To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS. This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS. This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION. Application of these recommendations should consider patients’ individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
- Published
- 2022
12. Association between low hemoglobin, clinical measures, and patient-reported outcomes in patients with rheumatoid arthritis: results from post hoc analyses of three phase III trials of sarilumab
- Author
-
Andrea, Rubbert-Roth, Daniel E, Furst, Stefano, Fiore, Amy, Praestgaard, Vivian, Bykerk, Clifton O, Bingham, Christina, Charles-Schoeman, and Gerd, Burmester
- Subjects
Arthritis, Rheumatoid ,Hemoglobins ,Methotrexate ,Treatment Outcome ,Antirheumatic Agents ,Adalimumab ,Humans ,Drug Therapy, Combination ,Patient Reported Outcome Measures ,Antibodies, Monoclonal, Humanized - Abstract
Background Anemia is common in patients with rheumatoid arthritis (RA). Higher hemoglobin (Hb) levels may be associated with better clinical outcomes and patient-reported outcomes (PROs). To assess this hypothesis, we conducted two post hoc analyses in three sarilumab phase III studies: TARGET, MOBILITY, and MONARCH. Methods Pooled data from combination therapy from placebo-controlled MOBILITY (sarilumab + methotrexate) and TARGET (sarilumab + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) and monotherapy data from active-controlled MONARCH (sarilumab vs. adalimumab) studies were included. Associations between Hb levels and clinical measures and PROs were assessed over 24 weeks. The mean changes from baseline in clinical outcomes and PROs (to week 24) and radiographic outcomes (to week 52) were evaluated between low and normal Hb levels (based on the World Health Organization [WHO] criteria). Results From TARGET, MOBILITY, and MONARCH, 546, 1197, and 369 patients, respectively, were stratified according to Hb levels (low vs. normal). Over 24 weeks, higher Hb levels were found to be consistently associated with better clinical outcomes and PROs in combination therapy and monotherapy groups and were more pronounced among the patients treated with sarilumab than those treated with placebo and adalimumab. The mean change from baseline to week 24 in clinical efficacy measures and PROs was similar in patients with low vs. normal Hb at baseline. Differences between sarilumab and/or adalimumab, for all outcomes, were larger for low Hb subgroups. In MOBILITY, by week 52, the inhibition of progression of structural damage (assessed via Modified Total Sharp Score [mTSS]) was 84% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with low Hb and 97% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with normal Hb. Similar results were observed for other radiographic outcomes. Conclusions In these post hoc analyses, a consistent relationship was observed between higher Hb levels and better clinical outcomes and PROs in patients with RA. Irrespective of the baseline Hb levels, sarilumab treatment was associated with improvements in clinical measures and PROs over 24 weeks (improvements were more pronounced than those with adalimumab treatment) and mitigation of joint damage progression over 52 weeks. Trial registration ClinTrials.gov NCT01061736, NCT01709578, and NCT02332590
- Published
- 2022
13. 'From Where I Stand': using multiple anchors yields different benchmarks for meaningful improvement and worsening in the rheumatoid arthritis flare questionnaire (RA-FQ)
- Author
-
Susan J, Bartlett, Vivian P, Bykerk, Orit, Schieir, Marie-France, Valois, Janet E, Pope, Gilles, Boire, Carol, Hitchon, Glen, Hazlewood, Louis, Bessette, Edward, Keystone, Carter, Thorne, Diane, Tin, Clifton O, Bingham, and M, Zummer
- Abstract
The Rheumatoid Arthritis Flare Questionnaire (RA-FQ) is a patient-reported measure of disease activity in RA. We estimated minimal and meaningful change from the perspective of RA patients, physicians, and using a disease activity index.Data were from 3- to 6-month visits of adults with early RA enrolled in the Canadian Early Arthritis Cohort. Participants completed the RA-FQ, the Patient Global Assessment of RA, and the Patient Global Change Impression at consecutive visits. Rheumatologists recorded joint counts and MD Global. Clinical Disease Activity Index (CDAI) scores were computed. We compared mean RA-FQ change across categories using patients, physicians, and CDAI anchors.The 808 adults were mostly white (84%) women (71%) with a mean age of 55 and moderate-high disease activity (85%) at enrollment. At V2, 79% of patients classified their RA as changed; 59% were better and 20% were worse. Patients reporting they were a lot worse had a mean RA-FQ increase of 8.9 points, whereas those who were a lot better had a -6.0 decrease. Minimal worsening and improvement were associated with a mean 4.7 and - 1.8 change in RA-FQ, respectively, while patients rating their RA unchanged had stable scores. Physician and CDAI classified more patients as worse than patients, and minimal and meaningful RA-FQ thresholds differed by group.Thresholds to identify meaningful change vary by anchor used. These data offer new evidence demonstrating robust psychometric properties of the RA-FQ and offer guidance about improvement or worsening, supporting its use in RA care, research, and decision-making.
- Published
- 2022
14. Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis
- Author
-
Anne R Bass, Noha Abdel-Wahab, Pankti D Reid, Jeffrey A Sparks, Cassandra Calabrese, Deanna P Jannat-Khah, Nilasha Ghosh, Divya Rajesh, Carlos Andres Aude, Lydia Gedmintas, Lindsey MacFarlane, Senada Arabelovic, Adewunmi Falohun, Komal Mushtaq, Farah Al Haj, Adi Diab, Ami A Shah, Clifton O Bingham, Karmela Kim Chan, and Laura C Cappelli
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
ObjectivesTo compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA).MethodsThe retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders.Results147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control.ConclusionThe treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.
- Published
- 2023
15. Conversion of Functional Assessment of Chronic Illness Therapy–Fatigue to Patient‐Reported Outcomes Measurement Information System Fatigue Scores in Two Phase III Baricitinib Rheumatoid Arthritis Trials
- Author
-
David Cella, Carol L Kannowski, Clifton O. Bingham, Amy M. DeLozier, Susan J. Bartlett, and Luna Sun
- Subjects
Adult ,Male ,Patient-Reported Outcomes Measurement Information System ,medicine.medical_specialty ,Time Factors ,Baricitinib ,Standard score ,Placebo ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Predictive Value of Tests ,Health Status Indicators ,Humans ,Janus Kinase Inhibitors ,Multicenter Studies as Topic ,Medicine ,Patient Reported Outcome Measures ,Fatigue ,Aged ,Randomized Controlled Trials as Topic ,030203 arthritis & rheumatology ,Sulfonamides ,business.industry ,Remission Induction ,Scoring methods ,Middle Aged ,medicine.disease ,humanities ,Clinical trial ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Purines ,Antirheumatic Agents ,Rheumatoid arthritis ,Chronic Disease ,Physical therapy ,Azetidines ,Pyrazoles ,Female ,Active treatment ,business - Abstract
OBJECTIVE The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is validated for measuring fatigue in rheumatoid arthritis (RA). However, 10 of 13 FACIT-F items are identified as relevant to patients with RA. The Patient-Reported Outcomes Measurement Information System (PROMIS) uses an item response theory-calibrated T score metric. The PROMIS Fatigue item bank includes the FACIT-F items, enabling score conversion. The performance of converted PROMIS Fatigue scores has not been evaluated in RA populations or clinical trials. Our objective was to assess the performance of converted PROMIS Fatigue scores in 2 RA clinical trials of baricitinib. METHODS Crosswalk tables and pattern-scoring methods converted FACIT-F scores to PROMIS Fatigue for both the 13-item FACIT-F and the 10-item RA-optimized FACIT-F instrument, in 2 RA clinical trials evaluating baricitinib, RA-BEAM, and RA-BEACON. RA-BEAM patients had an inadequate response to methotrexate. RA-BEACON patients had an inadequate response or intolerance to ≥1 tumor necrosis factor inhibitor. Baricitinib was compared to all treatment arms via analysis of covariance on PROMIS Fatigue score conversions. RESULTS Baseline FACIT-F-derived PROMIS Fatigue scores reflected severe fatigue across treatment groups and were similar using different scoring methods. At week 24 in both studies, baricitinib was associated with clinically meaningful improvements in PROMIS Fatigue scores. PROMIS Fatigue scores were consistent for conversion methods and for the 13-item or 10-item FACIT-F. CONCLUSION All 4 conversion methods showed differentiation of active treatment compared with placebo from week 12, supporting the use of the PROMIS Fatigue and converting the 10-item FACIT-F to assess fatigue and demonstrate treatment benefit in RA clinical trials on a standardized metric.
- Published
- 2021
16. Patients and clinicians define symptom levels and meaningful change for PROMIS pain interference and fatigue in RA using bookmarking
- Author
-
Susan J. Bartlett, Anne Lyddiatt, Clifton O. Bingham, Mary Suzanne Schrandt, Alessandra Butanis, Michelle Jones, Karon F. Cook, Ana Maria Orbai, Vivian P. Bykerk, and Victoria Ruffing
- Subjects
Adult ,Male ,medicine.medical_specialty ,Patient-Reported Outcomes Measurement Information System ,Pain Interference ,Severity of Illness Index ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Patient Reported Outcome Measures ,030212 general & internal medicine ,Fatigue ,Aged ,Pain Measurement ,030203 arthritis & rheumatology ,business.industry ,Bookmarking ,Lived experience ,Perspective (graphical) ,Middle Aged ,Clinical Science ,Social engagement ,Treatment efficacy ,Methotrexate ,Treatment Outcome ,Antirheumatic Agents ,Physical therapy ,Female ,Symptom Assessment ,business - Abstract
Objectives Using patient-reported outcomes to inform clinical decision-making depends on knowing how to interpret scores. Patient-Reported Outcome Measurement Information System® (PROMIS®) instruments are increasingly used in rheumatology research and care, but there is little information available to guide interpretation of scores. We sought to identify thresholds and meaningful change for PROMIS Pain Interference and Fatigue scores from the perspective of RA patients and clinicians. Methods We developed patient vignettes using the PROMIS item banks representing a continuum of Pain Interference and Fatigue levels. During a series of face-to-face ‘bookmarking’ sessions, patients and clinicians identified thresholds for mild, moderate and severe levels of symptoms and identified change deemed meaningful for making treatment decisions. Results In general, patients selected higher cut points to demarcate thresholds than clinicians. Patients and clinicians generally identified changes of 5–10 points as representing meaningful change. The thresholds and meaningful change scores of patients were grounded in their lived experiences having RA, approach to self-management, and the impacts on function, roles and social participation. Conclusion Results offer new information about how both patients and clinicians view RA symptoms and functional impacts. Results suggest that patients and providers may use different strategies to define and interpret RA symptoms, and select different thresholds when describing symptoms as mild, moderate or severe. The magnitude of symptom change selected by patients and clinicians as being clinically meaningful in interpreting treatment efficacy and loss of response may be greater than levels determined by external anchor and statistical methods.
- Published
- 2021
17. Understanding Differences in Patient Descriptions of Rheumatoid Arthritis Flares Using OMERACT Core Domains
- Author
-
Gabriela L. Maica, Christine Iannaccone, Vivi Feathers, Michelle L. Frits, Vivian P. Bykerk, Clifton O. Bingham, Michael Weinblatt, and Nancy A. Shadick
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy - Abstract
ObjectiveRecently, there has been consensus on domains that constitute flares in rheumatoid arthritis (RA); however, variations in patients' flare descriptions continue to be observed. This study evaluates how demographic and clinical characteristics influence these differences.MethodsParticipants enrolled in a prospective RA registry completed a qualitative survey that included the open-ended question "What does a flare mean to you?" Responses were categorized into Outcome Measures in Rheumatology (OMERACT) core and research domains. Univariate analyses evaluated demographic and clinical characteristics. Regression analyses determined independent variables associated with flare description variations.ResultsAmong 645 participants, the median Disease Activity Score in 28 joints (DAS28) with C-reactive protein was 2.1 (IQR 1.6-2.9); 58% of the participants reported at least 1 flare in the past 6 months. Participants reported a median of 3 (IQR 2-5) OMERACT domains when describing flares. Fatigue was more commonly noted among females (odds ratio [OR] 6.12;P< 0.001). Older participants were less likely to report emotional distress (OR 0.97;P= 0.03), swollen joints (OR 0.99;P= 0.04), physical function decrease (OR 0.98;P= 0.02), and a general increase in RA symptoms (OR 0.98;P= 0.005). Participants with a higher DAS28 score were less likely to report symptoms of stiffness (OR 0.70;P= 0.009), and those who experienced a flare within the last 6 months were more likely to describe flares as pain (OR 2.53;P< 0.001) and fatigue (OR 2.00;P= 0.007).ConclusionVariations in patients' flare descriptions can be driven by a patient's disease activity, the experience of a recent flare, as well as different demographic characteristics, such as age and gender. Understanding the interplay of these characteristics can guide a physician's approach to the management of patients' RA flares.
- Published
- 2023
18. Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group
- Author
-
Nilasha Ghosh, Nina Couette, Wouter H. van Binsbergen, Sophia C. Weinmann, Bridget Jivanelli, Beverley Shea, Anne R. Bass, Karolina Benesova, Clifton O. Bingham, Cassandra Calabrese, Laura C. Cappelli, Karmela Kim Chan, Ernest Choy, Dimitrios Daoussis, Susan Goodman, Marie Hudson, Shahin Jamal, Jan Leipe, Maria A. Lopez-Olivo, Maria Suarez-Almazor, Conny J. van der Laken, Alexa Simon Meara, David Liew, and Marie Kostine
- Subjects
Anesthesiology and Pain Medicine ,Rheumatology - Abstract
Introduction: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains. Methods: As the initial step of the core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter. Results: We identified 69 publications, over a third of which utilized non-specific diagnoses of “arthritis,” “arthralgia,” and/or “PMR”. Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 subsequent response, as well as 32 tumor response. Conclusion: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. There were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use.
- Published
- 2023
19. Association of Dysregulated Central Pain Processing and Response to Disease–Modifying Antirheumatic Drug Therapy in Rheumatoid Arthritis
- Author
-
Clifton O. Bingham, Andrew C. Heisler, Dorothy D. Dunlop, Wendy Marder, Daniel J. Clauw, Alyssa Wohlfahrt, Jing Song, Marcy B. Bolster, Lutfiyya N. Muhammad, Yvonne C. Lee, and Tuhina Neogi
- Subjects
Adult ,Male ,Pain Threshold ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Pain ,Arthritis ,Summation ,Logistic regression ,Article ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Disease-modifying antirheumatic drug ,Aged ,Pain Measurement ,030203 arthritis & rheumatology ,Central Nervous System Sensitization ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Antirheumatic Agents ,Rheumatoid arthritis ,Female ,business ,030217 neurology & neurosurgery ,Rheumatism - Abstract
Objective To determine the association between dysregulated central pain processing and treatment response in rheumatoid arthritis (RA). Methods One hundred eighty-two participants with active RA were followed up for 12 weeks after starting a disease-modifying antirheumatic drug (DMARD). To assess central pain processing, participants underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at the trapezius muscles, temporal summation, and conditioned pain modulation (CPM). QST measures were categorized as high central dysregulation versus low central dysregulation. The association between baseline central dysregulation and treatment response, as defined by the European League Against Rheumatism (EULAR) response criteria, was assessed using multiple logistic regression adjusted for demographic characteristics, RA-related variables, and psychosocial variables. Results A good EULAR response was achieved in fewer participants with high CPM dysregulation than participants with low CPM dysregulation (22.5% versus 40.3%; P = 0.01). A similar trend, though not significant, was noted when central dysregulation was assessed with PPT and temporal summation. The adjusted odds ratios (ORs) for the association between high central dysregulation and good EULAR response were 0.59 for PPTs (95% confidence interval [95% CI] 0.28-1.23), 0.60 for temporal summation (95% CI 0.27-1.34), and 0.40 for CPM (95% CI 0.19-0.83). In a model examining the combined effects of dysregulated temporal summation and CPM, dysregulation of both measures was associated with lower odds of achieving a good EULAR response (OR 0.23 [95% CI 0.07-0.73]). Conclusion Low CPM was significantly associated with lower odds of achieving a good EULAR response, suggesting that inefficient descending inhibitory mechanisms may be a potential treatment target for further study.
- Published
- 2020
20. What Does the Patient Global Health Assessment in Rheumatoid Arthritis Really Tell Us? Contribution of Specific Dimensions of Health‐Related Quality of Life
- Author
-
Ethan T. Craig, Jeffrey R. Curtis, Scott L. Zeger, Susan J. Bartlett, Clifton O. Bingham, Vivian P. Bykerk, and Jamie Perin
- Subjects
Adult ,Disease ,Article ,Arthritis, Rheumatoid ,Diagnostic Self Evaluation ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Rheumatology ,medicine ,Humans ,Patient Reported Outcome Measures ,Depression (differential diagnoses) ,Aged ,030203 arthritis & rheumatology ,Sleep disorder ,business.industry ,Middle Aged ,medicine.disease ,Mood ,Cohort ,Linear Models ,Quality of Life ,Anxiety ,Observational study ,medicine.symptom ,Factor Analysis, Statistical ,business ,Clinical psychology - Abstract
Objective To estimate the contributions of health-related quality of life domains to the patient global assessment of disease activity (PtGA) in rheumatoid arthritis (RA). Methods Data are drawn from baseline visits of 2 observational RA cohorts. Participants completed forms for patient-reported outcome measures, including PtGA and measures from the Patient-Reported Outcomes Measurement Information System, and clinical data were collected. Factor analysis was used to identify latent variables, and multivariable linear regression was used to estimate determinants of the PtGA. Results Patients were mostly female (81%), white (78%), and had established disease (mean ± SD 12.3 ± 10.7 years), with 62% in remission or having low disease activity. In cohort 1 (n = 196), the following 2 factors emerged: 1) daily function (moderate-to-strong [i.e., >|0.65|] loadings of physical function, pain interference, social participation, and fatigue, and weak [>0.35] loadings of sleep disturbance); and 2) emotional distress (strong loadings of depression and anxiety). In crude analysis, daily function explained up to 53% and emotional distress up to 20% of the variance in PtGA. In both cohorts, in adjusted analyses, daily function and, to a much lesser extent, swollen joint count independently predicted PtGA; age was inversely related to PtGA in cohort 1 only. Conclusion These findings suggest that in patients with RA, PtGA ratings largely reflect the extent to which patients feel they can function in everyday roles and are not impacted by mood. This suggests that higher than expected PtGA scores may offer an opportunity to discuss patient expectations regarding roles and activities and the impact of their RA symptoms on daily function.
- Published
- 2020
21. Reliability and validity of PROMIS physical function, pain interference, and fatigue as patient reported outcome measures in adult idiopathic inflammatory myopathies: International study from the OMERACT myositis working group
- Author
-
Dana DiRenzo, Didem Saygin, Ingrid de Groot, Clifton O. Bingham III, Ingrid E. Lundberg, Merrilee Needham, Jin Kyun Park, Malin Regardt, Catherine Sarver, Yeong Wook Song, Lara Maxwell, Dorcas Beaton, Marianne de Visser, Lisa Christopher-Stine, Christopher A. Mecoli, Helene Alexanderson, Neurology, AII - Infectious diseases, and Amsterdam Neuroscience - Neuroinfection & -inflammation
- Subjects
Anesthesiology and Pain Medicine ,Rheumatology - Abstract
Objective: Pain interference, fatigue, and impaired physical function are common features of idiopathic inflammatory myopathies (IIM). The objective of this study was to evaluate the construct validity and test-retest reliability of the Patient Reported Outcome Information System (PROMIS) Pain Interference 6av1.0, Fatigue 7av1.0, and Physical Function 8bv2.0 instruments. Methods: Patient-Reported Outcome Measures (PROMs) were deployed to adult IIM patients from OMERACT Myositis Working Group (MWG) international clinic sites via two online surveys (2019, 2021). Internal consistency of each PROM was analyzed by Cronbach's α. Construct validity was determined by a priori hypotheses generated by the MWG with >75% agreement for each hypothesis and calculated with Pearson correlations. Test-retest reliability was assessed using intraclass correlation coefficient with PROMIS instruments administered at time zero and 7 days. Results: Surveys were sent to 368 participants in total; participants who completed each questionnaire varied (n=65 to 263). For construct validity, 10 out of 13 a priori hypotheses were met supporting construct validity of PROMIS instruments (Pain Interference 3/4, fatigue 4/4, and Physical Function 3/5). Test-retest reliability was strong for all PROMIS instruments. All PROMIS instruments demonstrated excellent internal consistency. None of the measures demonstrated any ceiling or floor effects except for a ceiling effect in the Pain Interference instrument. Conclusions: This study presents test-retest reliability and construct validity evidence supporting PROMIS Pain Interference (6a v1.0), Fatigue (7a v1.0), and Physical Function (8b v2.0) using a large international cohort of patients with IIM. Internal consistency of these instruments was excellent. A ceiling effect was noted in the Pain Interference instrument.
- Published
- 2022
22. Association of Pain Centralization and Patient‐Reported Pain in Active Rheumatoid Arthritis
- Author
-
Dorothy D. Dunlop, Yvonne C. Lee, Clifton O. Bingham, Wendy Marder, Daniel J. Clauw, Jing Song, Alyssa Wohlfahrt, Marcy B. Bolster, Kristine Phillips, Tuhina Neogi, and Andrew C. Heisler
- Subjects
Adult ,Male ,Pain Threshold ,medicine.medical_specialty ,Arthritis ,Summation ,Article ,Arthritis, Rheumatoid ,Rheumatology ,Internal medicine ,Threshold of pain ,medicine ,Humans ,Patient Reported Outcome Measures ,Aged ,Pain Measurement ,Central Nervous System Sensitization ,business.industry ,Quantitative sensory testing ,Middle Aged ,medicine.disease ,Arthralgia ,Confidence interval ,Intensity (physics) ,Conditioned pain modulation ,Rheumatoid arthritis ,Linear Models ,Female ,business - Abstract
Objective Pain is a significant burden for patients with rheumatoid arthritis (RA) despite advancements in treatment. We undertook this study to examine the independent contribution of pain centralization to the pain experience of patients with active RA. Methods A total of 263 RA patients with active disease underwent quantitative sensory testing (QST), including assessment of extraarticular pressure pain thresholds (PPTs), temporal summation (TS), and conditioned pain modulation (CPM). The pain experience was assessed by a pain intensity numeric rating scale and the Patient-Reported Outcomes Measurement Information System pain interference computerized adaptive test. We examined associations between QST measures and pain intensity and pain interference. Multiple linear regression models were adjusted for demographic and clinical variables, including swollen joint count and C-reactive protein level. Results Patients with the lowest PPTs (most central dysregulation) reported higher pain intensity than patients with the highest PPTs (adjusted mean difference 1.02 [95% confidence interval (95% CI) 0.37, 1.67]). Patients with the highest TS (most central dysregulation) had higher pain intensity than those with the lowest TS (adjusted mean difference 1.19 [95% CI 0.54, 1.84]). CPM was not associated with differences in pain intensity. PPT and TS were not associated with pain interference. Patients with the lowest CPM (most centrally dysregulated) had lower pain interference than patients with the highest CPM (adjusted mean difference -2.35 [95% CI -4.25, -0.44]). Conclusion Pain centralization, manifested by low PPTs and high TS, was associated with more intense pain. Clinicians should consider pain centralization as a contributor to pain intensity, independent of inflammation.
- Published
- 2020
23. Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis
- Author
-
Laura C. Cappelli, Ami A. Shah, Clifton O. Bingham, Erika Darrah, and Mekha A. Thomas
- Subjects
0301 basic medicine ,Drug-Related Side Effects and Adverse Reactions ,Spondyloarthropathy ,Immune checkpoint inhibitors ,Inflammatory arthritis ,Immunology ,Biology ,medicine.disease_cause ,Article ,Autoimmune Diseases ,Autoimmunity ,Arthritis, Rheumatoid ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Animals ,Humans ,Immunology and Allergy ,Adverse effect ,Immune Checkpoint Inhibitors ,Arthritis ,Cancer ,Immune Checkpoint Proteins ,medicine.disease ,030104 developmental biology ,Rheumatoid arthritis ,030215 immunology - Abstract
The development of inflammatory arthritis in patients receiving immune checkpoint inhibitor therapy is increasingly recognized due to the growing use of these drugs for the treatment of cancer. This represents an important opportunity not only to define the mechanisms responsible for the development of this immune-related adverse event and to ultimately predict or prevent its development, but also to provide a unique window into early events in the development of inflammatory arthritis. Knowledge gained through the study of this patient population, for which the inciting event is known, could shed light into the pathogenesis of autoimmune arthritis. This review will highlight the clinical and immunologic features of these entities to define common elements for future study.
- Published
- 2020
24. Patient-reported outcomes in RA care improve patient communication, decision-making, satisfaction and confidence: qualitative results
- Author
-
Victoria Ruffing, Elaine De Leon, T. Duncan, Uzma Haque, Rebecca L. Manno, Alessandra Butanis, Jamie Perin, Amye Leong, Ana Maria Orbai, Susan J. Bartlett, Katherine Clegg Smith, Clifton O. Bingham, and M. Jones
- Subjects
Adult ,Male ,medicine.medical_specialty ,Attitude of Health Personnel ,Clinical Decision-Making ,Decision Making ,Disease ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Rheumatology ,Patient-Centered Care ,Humans ,Medicine ,Pharmacology (medical) ,Patient Reported Outcome Measures ,Prospective Studies ,030212 general & internal medicine ,Patient participation ,Prospective cohort study ,Qualitative Research ,Aged ,030203 arthritis & rheumatology ,Physician-Patient Relations ,business.industry ,Communication ,Middle Aged ,Clinical Science ,Focus group ,Patient Satisfaction ,Health Care Surveys ,Family medicine ,Female ,Patient communication ,Patient Participation ,business ,Psychosocial ,Qualitative research - Abstract
Objective To evaluate the impact of integrating patient-reported outcomes (PROs) into routine clinics, from the perspective of patients with RA, clinicians and other staff. Methods We conducted a prospective cohort study using a mixed methods sequential explanatory design at an academic arthritis clinic. RA patients completed selected Patient-Reported Outcomes Measurement Information System measures on tablets in the waiting room. Results were immediately available to discuss during the visit. Post-visit surveys with patients and physicians evaluated topics discussed and their impact on decision making; patients rated confidence in treatment. Focus groups or interviews with patients, treating rheumatologists and clinic staff were conducted to understand perspectives and experiences. Results Some 196 patients and 20 rheumatologists completed post-visit surveys at 816 and 806 visits, respectively. Focus groups were conducted with 24 patients, 10 rheumatologists and 4 research/clinic staff. PROs influenced medical decision-making and RA treatment changes (38 and 18% of visits, respectively). Patients reported very high satisfaction and treatment confidence. Impact on clinical workflow was minimal after a period of initial adjustment. PROs were valued by patients and physicians, and provided new insight into how patients felt and functioned over time. Reviewing results together improved communication, and facilitated patient-centred care, shared decision making, and the identification of new symptoms and contributing psychosocial/behavioural factors. Conclusion PRO use at RA visits was feasible, increased understanding of how disease affects how patients feel and function, facilitated shared decision-making, and was associated with high patient satisfaction and treatment confidence.
- Published
- 2019
25. Delphi panelists for a core outcome set project suggested both new and existing dissemination strategies that were feasibly implemented by a research infrastructure project
- Author
-
Alison E. Turnbull, Dale M. Needham, Victor D. Dinglas, Clifton O. Bingham, Caroline M. Chessare, and Ayodele A. Akinremi
- Subjects
Consensus ,Delphi Technique ,Information Dissemination ,Epidemiology ,Extramural ,Computer science ,business.industry ,Delphi method ,Outcome assessment ,Outcome (game theory) ,Set (abstract data type) ,Engineering management ,Core (game theory) ,Acute Disease ,Outcome Assessment, Health Care ,Health care ,Humans ,Respiratory Insufficiency ,business ,computer ,Delphi ,computer.programming_language - Published
- 2019
26. Anti-RA33 antibodies are present in a subset of patients with immune checkpoint inhibitor-induced inflammatory arthritis
- Author
-
Laura C. Cappelli, Patrick M. Forde, Clifton O. Bingham, Erika Darrah, Ami A. Shah, Jennifer S. Mammen, Megan D. Schollenberger, Julie R. Brahmer, Evan J. Lipson, and Valsamo Anagnostou
- Subjects
biology ,business.industry ,Immune checkpoint inhibitors ,Inflammatory arthritis ,Immunology ,medicine.disease ,Anti-Citrullinated Protein Antibodies ,Arthritis, Rheumatoid ,Rheumatology ,Rheumatoid Factor ,medicine ,biology.protein ,Immunology and Allergy ,Humans ,Antibody ,RA33 ,business ,Immune Checkpoint Inhibitors ,Autoantibodies - Abstract
ObjectivePatients with inflammatory arthritis (IA) associated with immune checkpoint inhibitor (ICI) treatment for cancer are typically seronegative for anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor, but little is known about the presence of other autoantibodies in this patient population. We investigated the prevalence and characteristics of anti-RA33 antibodies in patients with ICI-induced IA.MethodsAnti-RA33 ELISAs were performed on sera from four groups of patients: 79 with ICI-induced IA, 52 with rheumatoid arthritis (RA), 35 treated with ICIs without IA during follow-up and 50 healthy controls. Anti-RA33 positivity and level, clinical and demographic data were compared across groups.ResultsAnti-RA33 antibodies were found in 9/79 (11.4%) patients with ICI-induced IA but in 0/35 patients treated with ICIs who did not develop IA (0%; p=0.04). Of the patients positive for anti-RA33, two had sera available from before ICI treatment; anti-RA33 antibodies were present in both pre-ICI treatments. In patients with RA, 7.7% were positive for anti-RA33 antibodies as were 2% of healthy controls. In ICI-induced IA, anti-RA33 antibodies were associated with anti-CCP antibodies (p=0.001). We found no statistically significant differences in other clinical characteristics in those with and without anti-RA33 antibodies.ConclusionsAnti-RA33 antibodies are present in a subset of patients with ICI-induced IA, absent in other ICI-treated patients and may be a biomarker for developing IA. Additional studies evaluating serial samples before and after ICI treatment will further establish the temporal relationship of these antibodies to IA development.
- Published
- 2021
27. Autoantibodies targeting telomere-associated proteins in systemic sclerosis
- Author
-
Ami A. Shah, Clifton O. Bingham, Carol W. Greider, Livia Casciola-Rosen, Francesco Boin, Brittany L. Adler, Paul J. Wolters, and Antony Rosen
- Subjects
0301 basic medicine ,Male ,Telomerase ,autoantibodies ,Pulmonary Fibrosis ,Autoimmunity ,Autoantigens ,Scleroderma ,Shelterin Complex ,Pathogenesis ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Pulmonary fibrosis ,Immunology and Allergy ,2.1 Biological and endogenous factors ,scleroderma ,Aetiology ,Lung ,Middle Aged ,Telomere ,Respiratory ,Public Health and Health Services ,Female ,Adult ,Telomere-Binding Proteins ,Clinical Sciences ,Immunology ,Autoimmune Disease ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Rare Diseases ,Rheumatology ,Clinical Research ,medicine ,Humans ,Autoantibodies ,Aged ,030203 arthritis & rheumatology ,Scleroderma, Systemic ,pulmonary fibrosis ,business.industry ,Inflammatory and immune system ,Autoantibody ,systemic ,medicine.disease ,Shelterin ,Fibrosis ,Idiopathic Pulmonary Fibrosis ,Arthritis & Rheumatology ,030104 developmental biology ,business - Abstract
ObjectivesSystemic sclerosis (SSc) is an autoimmune fibrotic disease affecting multiple tissues including the lung. A subset of patients with SSc with lung disease exhibit short telomeres in circulating lymphocytes, but the mechanisms underlying this observation are unclear.MethodsSera from the Johns Hopkins and University of California, San Francisco (UCSF) Scleroderma Centers were screened for autoantibodies targeting telomerase and the shelterin proteins using immunoprecipitation and ELISA. We determined the relationship between autoantibodies targeting the shelterin protein TERF1 and telomere length in peripheral leucocytes measured by qPCR and flow cytometry and fluorescent in situ hybridisation (Flow-FISH). We also explored clinical associations of these autoantibodies.ResultsIn a subset of patients with SSc, we identified autoantibodies targeting telomerase and the shelterin proteins that were rarely present in rheumatoid arthritis, myositis and healthy controls. TERF1 autoantibodies were present in 40/442 (9.0%) patients with SSc and were associated with severe lung disease (OR 2.4, p=0.04, Fisher’s exact test) and short lymphocyte telomere length. 6/6 (100%) patients with TERF1 autoantibodies in the Hopkins cohort and 14/18 (78%) patients in the UCSF cohort had a shorter telomere length in lymphocytes or leukocytes, respectively, relative to the expected age-adjusted telomere length. TERF1 autoantibodies were present in 11/152 (7.2%) patients with idiopathic pulmonary fibrosis (IPF), a fibrotic lung disease believed to be mediated by telomere dysfunction.ConclusionsAutoantibodies targeting telomere-associated proteins in a subset of patients with SSc are associated with short lymphocyte telomere length and lung disease. The specificity of these autoantibodies for SSc and IPF suggests that telomere dysfunction may have a distinct role in the pathogenesis of SSc and pulmonary fibrosis.
- Published
- 2021
28. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials
- Author
-
Susan J. Bartlett, Clifton O. Bingham, Ronald van Vollenhoven, Christopher Murray, David Gruben, David A. Gold, David Cella, Rheumatology, AII - Inflammatory diseases, Clinical Immunology and Rheumatology, and AMS - Musculoskeletal Health
- Subjects
Patient-reported outcomes ,Health-related quality of life ,Vitality ,humanities ,Arthritis, Rheumatoid ,Methotrexate ,Pyrimidines ,Treatment Outcome ,Piperidines ,Tofacitinib ,Antirheumatic Agents ,Quality of Life ,Humans ,Pyrroles ,Rheumatoid arthritis ,Sleep ,Fatigue - Abstract
Background Fatigue, a common symptom of rheumatoid arthritis (RA), is detrimental to health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on fatigue, sleep, and HRQoL and explored associations between fatigue, related patient-reported outcomes (PROs), and disease activity in RA patients. Methods This post hoc analysis pooled data from three Phase 3 studies of tofacitinib (ORAL Scan; ORAL Standard; ORAL Sync) in RA patients. Patients received tofacitinib 5 or 10 mg twice daily, placebo, or adalimumab (active control; ORAL Standard only, not powered for superiority) with conventional synthetic disease-modifying antirheumatic drugs. Assessed through Month (M)12 were changes from baseline in disease activity, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Medical Outcomes Study Sleep scale (MOS-SS), and Short Form-36 Health Survey (SF-36) composite/domain scores, and proportions of patients reporting improvements from baseline in FACIT-F total and SF-36 domain scores ≥ minimum clinically important differences (MCIDs) or ≥ population normative values. Pearson correlations examined associations among PROs at M6. Treatment comparisons were exploratory, with p < 0.05 considered nominally significant. Results Generally, active treatment led to significant improvements from baseline in FACIT-F total, and MOS-SS and SF-36 composite/domain scores vs placebo, observed by M1 and maintained through M6 (last placebo-controlled time point). Through M6, more patients achieved improvements from baseline ≥ MCID and achieved scores ≥ population normative values in FACIT-F total and SF-36 domain scores with tofacitinib vs placebo. Through M12, some nominally significant improvements with tofacitinib vs adalimumab were observed. With active treatment at M6, FACIT-F scores were moderately (0.40–0.59) to highly (≥ 0.60) correlated with SF-36 composite/domain scores (particularly vitality), moderately correlated with most MOS-SS domain scores, and highly correlated with MOS-SS Sleep Problems Index I scores. Disease activity correlations were moderate with FACIT-F scores and low (0.20–0.39) to moderate with SF-36 general health domain/composite scores. Conclusion Tofacitinib and adalimumab generally conferred significant, clinically meaningful improvements in fatigue, sleep, and HRQoL (including vitality) vs placebo through M6, with improvements maintained to M12. M6 correlations between FACIT-F, PROs of sleep, HRQoL, and disease activity underscore the interrelatedness of multiple PROs and disease activity in RA. Trial registration ClinicalTrials.govNCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009).
- Published
- 2021
29. Feasibility and acceptability of using a meditation app in adults with rheumatic disease
- Author
-
Ami A. Shah, Carly Hunt, Neda F Gould, Clifton O. Bingham, Susan J. Bartlett, Dana DiRenzo, and Erica Ms Sibinga
- Subjects
Adult ,medicine.medical_specialty ,media_common.quotation_subject ,Pilot Projects ,NIH Toolbox ,Rheumatic Diseases ,Medicine ,Humans ,Meditation ,General Nursing ,Fatigue ,media_common ,Sleep disorder ,business.industry ,Rheumatic disease ,Mean age ,Middle Aged ,medicine.disease ,Intervention studies ,Mobile Applications ,Chronic disease ,Complementary and alternative medicine ,Physical therapy ,Quality of Life ,Anxiety ,Feasibility Studies ,Female ,Chiropractics ,medicine.symptom ,business ,Analysis - Abstract
OBJECTIVE Meditation is a stress-reduction and contemplative technique that can improve emotional distress in people with chronic disease and may be especially beneficial for patients with rheumatic diseases. However, patient access to in-person programs is challenging. The goal of this pilot study was to evaluate the feasibility/acceptability associated with physician-directed use of a widely available smartphone application (app), Calm©. METHODS In this single-arm, pre-post intervention study with recruitment over a 10-month period, adults with rheumatic disease were asked to use the app for ≥5 min/day for 30 days. Participants completed sociodemographic surveys and validated health related quality of life (HRQL) questionnaires from the Patient Reported Outcomes Information System (PROMIS) and NIH Toolbox at baseline and 30-days. RESULTS Thirty-five participants who were mostly well-educated (66% ≥college degree) females (91%) with a mean age of 50 (SD 13) completed baseline questionnaires; 18 participants completed post-study questionnaires ("full completers"). Full completers had higher baseline stress, anxiety, pain, and patient global assessment scores (p's
- Published
- 2021
30. Development of a patient-centered core domain set for prospective observational longitudinal outcome studies in rheumatoid arthritis: an OMERACT initiative
- Author
-
Tiffany Westrich-Robertson, Niti Goel, Clifton O. Bingham, Maria E. Suarez-Almazor, Loreto Carmona, Beverley Shea, Sebastian Bruera, Christopher Hill, Peter Tugwell, Vibeke Strand, Robin Christensen, Lyn March, Amye Leong, Maria A. Lopez-Olivo, Jose B. Negron, and Francesca Ingegnoli
- Subjects
rheumatoid arthritis ,medicine.medical_specialty ,Consensus ,Delphi method ,Outcome (game theory) ,Core domain ,Domain (software engineering) ,Arthritis, Rheumatoid ,Rheumatology ,cohort studies ,patient-centered outcomes ,Patient-Centered Care ,Outcome Assessment, Health Care ,medicine ,Humans ,Medical physics ,Prospective Studies ,Set (psychology) ,observational studies ,business.industry ,Patient-centered outcomes ,OMERACT ,patient registries ,medicine.disease ,Anesthesiology and Pain Medicine ,Rheumatoid arthritis ,Observational study ,business - Abstract
Objectives To identify patient-centered core domains for prospective longitudinal observational studies (LOS) in rheumatoid arthritis. Methods Our working group held a virtual meeting in November 2020 to review data from a literature review and patient qualitative interviews, and to discuss strategies to move forward on domain identification and selection using the OMERACT 2.1 domain selection process. Results Important candidate domains and subdomains were identified including in the areas of life impact. Consensus was reached on moving forward with a Delphi process. Conclusions The meeting provided future directions to identify and select a core set of domains for use in LOS.
- Published
- 2021
31. OMERACT 2020: A virtual (R)evolution
- Author
-
Jasvinder A. Singh, Catherine Hofstetter, Lee S. Simon, Lyn March, Peter Tugwell, Phil Conaghan, George A. Wells, Bev Shea, Dorcas E. Beaton, Maria Antonietta D'Agostino, Clifton O. Bingham, Vibeke Strand, Lara J Maxwell, and Shawna Grosskleg
- Subjects
Anesthesiology and Pain Medicine ,Information retrieval ,Text mining ,Rheumatology ,business.industry ,Rheumatic Diseases ,MEDLINE ,Medicine ,Humans ,business - Published
- 2021
32. The Relationship Between Autonomic Dysfunction of the Gastrointestinal Tract and Emotional Distress in Patients With Systemic Sclerosis
- Author
-
James W. Russell, Dana DiRenzo, Clifton O. Bingham, and Zsuzsanna H. McMahan
- Subjects
Male ,medicine.medical_specialty ,Gastrointestinal Diseases ,Autonomic Nervous System ,Psychological Distress ,Logistic regression ,Severity of Illness Index ,Article ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Severity of illness ,Humans ,Medicine ,030212 general & internal medicine ,Prospective cohort study ,Autoantibodies ,030203 arthritis & rheumatology ,Univariate analysis ,Scleroderma, Systemic ,Exosome Multienzyme Ribonuclease Complex ,business.industry ,Confounding ,Dysautonomia ,Odds ratio ,Middle Aged ,United States ,Gastrointestinal Tract ,Clinical trial ,Autonomic Nervous System Diseases ,Research Design ,Exoribonucleases ,Female ,Symptom Assessment ,medicine.symptom ,business - Abstract
BACKGROUND/OBJECTIVES We hypothesized that emotional distress in systemic sclerosis (SSc) patients with moderate to severe gastrointestinal (GI) dysfunction is associated with dysautonomia. We sought to determine (1) the clinical characteristics associated with emotional distress in SSc, (2) the odds of having dysautonomia in those with emotional distress, and (3) whether GI dysautonomia, as measured by the Survey of Autonomic Symptoms (SAS), correlates with GI dysautonomia on the Composite Autonomic Symptom Score-31 (COMPASS-31). METHODS Clinical and demographic features from our prospective cohort study were compared among SSc patients with and without GI-associated emotional distress (University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 well-being subscale >0.5 or ≤0.5) in cross-sectional analysis. Covariates/confounders independently associated with emotional distress were used to construct multivariable logistic regression models. The COMPASS-31 and SAS GI subdomains were compared with Spearman correlation. RESULTS Forty-six patients with SSc were enrolled in the study. In univariate analyses, age (odds ratio [OR], 1.06; p = 0.026), severity of GI dysautonomia (COMPASS-31: OR, 1.41; p = 0.003), anti-centromere (A/B) antibodies (OR, 3.60; p = 0.044), and anti-PM-Scl (75/100) antibodies (OR, 0.15; p = 0.035) were associated with emotional distress. In the adjusted model, those with more severe GI dysautonomia remained more likely to have emotional distress (OR, 1.85; p = 0.026); those with anti-PM-Scl (75/100) antibodies were less likely to have emotional distress (OR, 0.03; p = 0.031). The SAS and COMPASS-31 GI subdomains moderately correlated (ρ = 0.68, p < 0.001). CONCLUSIONS In SSc, increased symptom burden related to GI dysautonomia is associated with emotional distress. Multidisciplinary approaches addressing both the physical and emotional needs of the SSc patient may be warranted to optimize patient care.
- Published
- 2019
33. A Multidisciplinary Toxicity Team for Cancer Immunotherapy–Related Adverse Events
- Author
-
John C. Probasco, Amy K. Kim, Ami A. Shah, Jennifer E. Thorne, Rosanne Rouf, Alyssa Parian, Jiajia Zhang, Laura C. Cappelli, Satish Shanbhag, Evan J. Lipson, Julie R. Brahmer, Shawn G. Kwatra, Karthik Suresh, Clifton O. Bingham, Jarushka Naidoo, Patrick M. Forde, Kendall F. Moseley, Seema Mehta, Drew M. Pardoll, and Joanne Riemer
- Subjects
Adult ,Male ,Program evaluation ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Referral ,MEDLINE ,Pilot Projects ,Cancer Care Facilities ,Medical Oncology ,Toxicology ,Tertiary Care Centers ,Young Adult ,Antineoplastic Agents, Immunological ,Multidisciplinary approach ,Neoplasms ,Humans ,Medicine ,Young adult ,Adverse effect ,Intersectoral Collaboration ,Referral and Consultation ,Aged ,Pneumonitis ,Aged, 80 and over ,Patient Care Team ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Oncology ,Emergency medicine ,Feasibility Studies ,Female ,business ,Program Evaluation - Abstract
Background: Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs). Methods to obtain real-time multidisciplinary input for irAEs that require subspecialist care are unknown. This study aimed to determine whether a virtual multidisciplinary immune-related toxicity (IR-tox) team of oncology and medicine subspecialists would be feasible to implement, be used by oncology providers, and identify patients for whom multidisciplinary input is sought. Patients and Methods: Patients treated with ICIs and referred to the IR-tox team in August 2017 through March 2018 were identified. Feasibility was defined as receipt of electronic referrals and provision of recommendations within 24 hours of referral. Use was defined as the proportion of referring providers who used the team’s recommendations, which was determined through a postpilot survey. Demographics and tumor, treatment, and referral data were collected. Patient features and irAE associations were analyzed. Results: The IR-tox team was found to be feasible and used: 117 referrals from 102 patients were received in 8 months, all providers received recommendations within 24 hours, 100% of surveyed providers used the recommendations, and 74% changed patient management based on IR-tox team recommendations. Referrals were for suspected irAEs (n=106; 91%) and suitability to treat with ICIs (n=11; 10%). In referred patients, median age was 64 years, 54% were men, 13% had prior autoimmunity, and 46% received ICI combinations versus monotherapy (54%). The most commonly referred toxicities were pneumonitis (23%), arthritis (16%), and dermatitis (15%); 15% of patients had multisystem toxicities. Multiple referrals were more common in those treated with combination ICIs (odds ratio [OR], 6.0; P=.035) or with multisystem toxicities (OR, 8.1; P=.005). The IR-tox team provided a new multidisciplinary forum to assist providers in diagnosing and managing complex irAEs. This model identifies educational and service needs, and patients with irAEs for whom multidisciplinary care is most sought. Conclusions: A virtual multidisciplinary toxicity team for irAEs was a feasible and used service, and facilitated toxicity identification and management.
- Published
- 2019
34. Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis
- Author
-
Stephen Desiderio, Gustavo Nino, Maria J. Gutierrez, Erika Darrah, Nae Yuh Wang, Clifton O. Bingham, Laura C. Cappelli, and Michelle Jones
- Subjects
Male ,Arthritis ,Lymphocyte Activation ,medicine.disease_cause ,Arthritis, Rheumatoid ,0302 clinical medicine ,Immunology and Allergy ,B-Lymphocytes ,0303 health sciences ,biology ,General Medicine ,Middle Aged ,3. Good health ,Rheumatoid arthritis ,Female ,Antibody ,Research Article ,medicine.drug ,lcsh:Immunologic diseases. Allergy ,Adult ,Risk ,Article Subject ,Adolescent ,Cell Survival ,Tumor Necrosis Factor Ligand Superfamily Member 13 ,Immunology ,Infections ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,B-Cell Maturation Antigen ,CD40 Antigens ,CXCL13 ,Antibody-Producing Cells ,B-cell activating factor ,Aged ,Autoantibodies ,Retrospective Studies ,030304 developmental biology ,030203 arthritis & rheumatology ,business.industry ,Autoantibody ,Immune dysregulation ,medicine.disease ,United States ,biology.protein ,Methotrexate ,lcsh:RC581-607 ,business ,Biomarkers - Abstract
Background. Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with immune dysregulation and increased risk of infections. The presence of autoantibodies and immunoglobulin abnormalities indicates B-cell and antibody-secreting cell (ASC) dysfunction. We hypothesize that soluble factors associated with B-cell and ASC activity are decreased in RA patients and that this is linked to higher susceptibility to infections.Methods. Using the Johns Hopkins Arthritis Cohort and Biorepository, we contrasted serum protein levels of soluble factors involved in B-cell activation (CD40, CD40L) and B-cell/ASC homing (CXCL10, CXCL11, and CXCL13) or survival (BAFF, APRIL, TACI, and BCMA) in 10 healthy subjects and 23 adult RA patients (aged 24-65 years). We subdivided RA patients into those with (n=17) and those without infections (n=6) within a 2-year period. In order to reduce the effect of RA treatment, we only included patients receiving methotrexate monotherapy or no RA treatments at baseline. Soluble serum protein levels of B-cell/ASC factors were quantified by multiplex immunoassays.Results. We identified that (1) serum levels of soluble BCMA, APRIL, CD40, and CD40L were significantly decreased in RA patients relative to healthy individuals; (2) serum soluble BCMA, predominantly released by ASC, correlated with serum concentrations of class-switched immunoglobulins, IgG and IgA; and (3) RA patients with a history of infections had significantly lower soluble BCMA levels compared with healthy donors and with RA patients without infections.Conclusions. Our study using soluble factors linked to B-cell/ASC activation and survival suggests that there is a paucity of ASC in a subset of RA patients and that this may be linked to altered antibody production and increased risk of infections. Further delineating the link between ASC and infection susceptibility in RA may optimize disease management and provide novel insights into disease pathogenesis that are susceptible to intervention.
- Published
- 2019
35. Responsiveness of Patient‐Reported Outcomes Measurement Information System Measures in Rheumatoid Arthritis Patients Starting or Switching a Disease‐Modifying Antirheumatic Drug
- Author
-
Clifton O. Bingham, Yvonne C. Lee, Zhi Zhang, Larry W. Moreland, Kristine Phillips, Alyssa Wohlfahrt, Marcy B. Bolster, Tuhina Neogi, and Wendy Marder
- Subjects
Adult ,Male ,medicine.medical_specialty ,Patient-Reported Outcomes Measurement Information System ,medicine.medical_treatment ,Item bank ,Arthritis ,Article ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,medicine ,Humans ,Patient Reported Outcome Measures ,Prospective Studies ,Disease-modifying antirheumatic drug ,skin and connective tissue diseases ,Prospective cohort study ,Depression (differential diagnoses) ,Aged ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,Antirheumatic Agents ,Rheumatoid arthritis ,Physical therapy ,Female ,Observational study ,business - Abstract
Objective The Patient-Reported Outcomes Measurement Information System (PROMIS) is a calibrated item bank used to assess patient-reported outcomes across multiple domains. The purpose of this study was to describe the performance of selected PROMIS measures in patients with rheumatoid arthritis (RA) with active disease who were initiating a disease-modifying antirheumatic drug (DMARD). Methods Participants in an ongoing prospective observational study completed 8 PROMIS measures before and after DMARD initiation. Linear regression models were performed to identify cross-sectional associations between baseline PROMIS measures and disease activity, measured using the Clinical Disease Activity Index (CDAI). Paired t-tests were performed to evaluate responsiveness after 12 weeks of DMARD treatment. Associations between changes in PROMIS measures and changes in the CDAI score were assessed using linear regression. Results Among the 156 participants who completed the first study visit, the mean ± SD baseline CDAI score was 25.5 ± 14.0. Baseline scores for PROMIS measures of physical health, pain, and sleep were associated with the baseline CDAI score (P ≤ 0.05). Among the 106 participants with 12-week data, all PROMIS scores improved after DMARD initiation (P ≤ 0.05). With the exception of depression, changes in all assessed PROMIS measures were correlated with changes in the CDAI score (standardized βs from |0.23| to |0.38|). Conclusion These data provide support for the utility of PROMIS measures for the assessment of physical and mental health in individuals with active RA. All PROMIS measures improved significantly after DMARD initiation, with the magnitudes of association between changes in PROMIS measures and changes in the CDAI score in the low-to-moderate range.
- Published
- 2019
36. OMERACT 2018 Modified Patient-reported Outcome Domain Core Set in the Life Impact Area for Adult Idiopathic Inflammatory Myopathies
- Author
-
Ingrid de Groot, Jin Kyun Park, Catherine Sarver, Beverly Shea, Christopher A. Mecoli, Lisa Christopher-Stine, Helene Alexanderson, Merrilee Needham, Marianne de Visser, Clifton O. Bingham, Yeong W. Song, Malin Regardt, and Ingrid E. Lundberg
- Subjects
Adult ,Male ,medicine.medical_specialty ,Consensus ,Delphi Technique ,Immunology ,Pain ,Severity of Illness Index ,Domain (software engineering) ,Rheumatology ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Immunology and Allergy ,Patient Reported Outcome Measures ,Set (psychology) ,Exercise ,Impact area ,Fatigue ,Myositis ,Aged ,Core set ,business.industry ,Focus Groups ,Middle Aged ,medicine.disease ,Treatment Outcome ,Idiopathic inflammatory myopathies ,Quality of Life ,Physical therapy ,Female ,Patient-reported outcome ,business - Abstract
Objective.To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018.Methods.Based on results from international focus groups and Delphi surveys, a draft core set was developed.Results.Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018.Conclusion.We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.
- Published
- 2019
37. Establishing an Updated Core Domain Set for Studies in Juvenile Idiopathic Arthritis: A Report from the OMERACT 2018 JIA Workshop
- Author
-
Karine Toupin-April, Julia G. Harris, Jelena Vojinovic, Marion A J van Rossum, Silvia Magni-Manzoni, Beverley Shea, Esi M. Morgan, Nicolino Ruperto, Richard Vesely, Angelo Ravelli, Daniel B. Horton, Brian M. Feldman, Clifton O. Bingham, Pamela F. Weiss, Susan Shenoi, Jennifer Horonjeff, Vibeke Strand, Nikolay Tzaribachev, Homaira Rahimi, Jane E Munro, Melissa L. Mannion, Natalie J. Shiff, Daniel J. Lovell, Alessandro Consolaro, Susan Thornhill, Sarah Ringold, Ben Horgan, Alessandra Alongi, M. Suzanne Schrandt, Hermine I. Brunner, Hayyah Clairman, General Paediatrics, and AII - Inflammatory diseases
- Subjects
musculoskeletal diseases ,Male ,medicine.medical_specialty ,Adolescent ,Immunology ,Delphi method ,ODB++ ,law.invention ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Randomized controlled trial ,Quality of life ,law ,Outcome Assessment, Health Care ,medicine ,Humans ,Immunology and Allergy ,Patient Reported Outcome Measures ,030212 general & internal medicine ,030203 arthritis & rheumatology ,Response rate (survey) ,Clinical Trials as Topic ,business.industry ,Australia ,Special Interest Group ,Arthritis, Juvenile ,United States ,Clinical trial ,Treatment Outcome ,Italy ,Antirheumatic Agents ,Family medicine ,Female ,Observational study ,business - Abstract
Objective.The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting.Methods.Candidate domains were identified through literature review, qualitative surveys, and online discussion boards (ODB) held with patients with JIA and parents in Australia, Italy, and the United States. A Delphi process with parents, patients, healthcare providers, researchers, and regulators served to edit the domain list and prioritize candidate domains. After the presentation of results, OMERACT workshop participants voted, with consensus set at > 70%.Results.Participants in ODB were 53 patients with JIA (ages 15–24 yrs) and 55 parents. Three rounds of Delphi considering 27 domains were completed by 190 (response rate 85%), 201 (84%), and 182 (77%) people, respectively, from 50 countries. There was discordance noted between domains prioritized by patients/parents compared to others. OMERACT conference voting approved domains for JIA RCT and LOS with 83% endorsement. Mandatory domains are pain, joint inflammatory signs, activity limitation/physical function, patient’s perception of disease activity (overall well-being), and adverse events. Mandatory in specific circumstances: inflammation/other features relevant to specific JIA categories.Conclusion.Following the OMERACT methodology, we developed an updated JIA Core Domain Set. Next steps are to identify and systematically evaluate best outcome measures for these domains.
- Published
- 2019
38. 292 Fibromyalgianess and Glucocorticoid Persistence Among Patients with Rheumatoid Arthritis
- Author
-
Beth Wallace, Meriah N. Moore, Andrew C. Heisler, Lutfiyya N. Muhammad, Jing Song, Daniel J. Clauw, Clifton O. Bingham, Marcy B. Bolster, Wendy Marder, Tuhina Neogi, Alyssa Wohlfahrt, Dorothy D. Dunlop, and Yvonne C. Lee
- Subjects
musculoskeletal diseases ,General Medicine ,humanities - Abstract
OBJECTIVES/GOALS: Over 30% of patients with rheumatoid arthritis (RA) exhibit fibromyalgianess, a symptom cluster associated with increased pain sensitivity. Up to half of RA patients use oral glucocorticoids (GCs) long-term despite their known, dose-dependent toxicity. We examined the association between fibromyalgianess and oral GC persistence in RA patients. METHODS/STUDY POPULATION: We used data from the Central Pain in Rheumatoid Arthritis (CPIRA) cohort to follow participants with active RA on oral prednisone who initiated a new disease-modifying anti-rheumatic drug. We measured fibromyalgianess using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key fibromyalgia features often superimposed upon RA. We stratified fibromyalgianess severity as follows: FSQ10 high/very high. We defined GC persistence as GC use at 3 month followup visit. We assessed the association between baseline fibromyalgianess (exposure) and GC persistence at followup (outcome) using multiple logistic regression, adjusted for demographics, RA duration, serostatus, and inflammatory activity measured by swollen joint count and C reactive protein. RESULTS/ANTICIPATED RESULTS: Of 97 participants on prednisone at baseline, 65% were taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent GC use, compared to 84% with high or very high fibromyalgianess. After adjustment as outlined above, participants with high/very high baseline fibromyalgianess remained more likely to be on prednisone at follow-up, relative to those with low fibromyalgianess (OR 4.99 [95% CI 1.20 – 20.73]). DISCUSSION/SIGNIFICANCE: In this cohort of patients with active RA, high fibromyalgianess is associated with persistent GC use, independent of inflammatory activity. This finding suggests non-inflammatory pain related to fibromyalgianess may be misclassified as inflammatory pain related to RA disease activity.
- Published
- 2022
39. Successful Methotrexate Treatment of Chronic Chikungunya Arthritis
- Author
-
Robert T. Schoen, Clifton O. Bingham, and J. Kennedy Amaral
- Subjects
030203 arthritis & rheumatology ,Methotrexate treatment ,medicine.medical_specialty ,business.industry ,Arthritis ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,030212 general & internal medicine ,Chikungunya ,business - Published
- 2018
40. Phenotypic characterization of patients with rheumatologic manifestations of common variable immunodeficiency
- Author
-
Ramsay Fuleihan, Kathleen E. Sullivan, Clifton O. Bingham, and Maria J. Gutierrez
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Autoimmunity ,Logistic regression ,medicine.disease_cause ,Article ,Young Adult ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Immunophenotyping ,Immune system ,Rheumatology ,Internal medicine ,medicine ,Humans ,Registries ,Child ,Immunodeficiency ,Aged ,Retrospective Studies ,Aged, 80 and over ,030203 arthritis & rheumatology ,business.industry ,Common variable immunodeficiency ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Phenotype ,Common Variable Immunodeficiency ,030104 developmental biology ,Anesthesiology and Pain Medicine ,Child, Preschool ,Female ,Symptom Assessment ,business - Abstract
Patients with common variable immunodeficiency (CVID) have a higher incidence of rheumatologic disorders. To delineate this clinical association, we investigated the phenotypic features of patients with CVID affected by these conditions. METHODS: We conducted a retrospective analysis of 870 pediatric and adult patients with CVID included in the United States Immunodeficiency Network (USIDNET) registry. Outcomes included clinical characteristics (age, gender, ethnicity, rheumatologic diagnosis, comorbidities), infectious history and basic immunophenotype (serum immunoglobulin levels, CD19+ B cells and CD4/CD8 ratio) in patients with CVID and rheumatologic disorders compared to those with non-inflammatory CVID. Demographic and clinical data were compared using chi-square, Fisher’s exact or Wilcoxon-Mann-Whitney tests. Non-parametric tests, single and multiple logistic regression models were used to evaluate the relationship between CVID-associated rheumatologic disorders and basic immunophenotypic parameters (IgA, IgM, CD19+ B-cell counts and CD4/CD8 ratios) RESULTS: Physician-reported rheumatic diseases were present in 5.9% of patients with CVID (n=51) included in the registry. Although CVID affects both sexes equally, and patients are of predominantly White-Caucasian ethnicity, there were more females (3.3:1 female to male ratio) and increased proportion of non-white patients in the rheumatologic disease group (p
- Published
- 2018
41. A survey of Delphi panelists after core outcome set development revealed positive feedback and methods to facilitate panel member participation
- Author
-
Clifton O. Bingham, Victor D. Dinglas, Lisa Aronson Friedman, Caroline M. Chessare, Alison E. Turnbull, Dale M. Needham, and Kristin A. Sepulveda
- Subjects
Adult ,Male ,medicine.medical_specialty ,Consensus ,Delphi Technique ,Epidemiology ,media_common.quotation_subject ,education ,Delphi method ,Outcome (game theory) ,Feedback ,Young Adult ,03 medical and health sciences ,Age Distribution ,0302 clinical medicine ,Surveys and Questionnaires ,Voting ,Outcome Assessment, Health Care ,medicine ,Humans ,Survivors ,030212 general & internal medicine ,Set (psychology) ,Aged ,computer.programming_language ,media_common ,Stakeholder ,Middle Aged ,Core (game theory) ,Family medicine ,Female ,Professional association ,Respiratory Insufficiency ,Psychology ,computer ,030217 neurology & neurosurgery ,Delphi - Abstract
Objectives The objective of this study was to elicit feedback on consensus methodology used for core outcome set (COS) development. Study Design and Setting An online survey of international Delphi panelists participating in a recent COS for clinical research studies evaluating acute respiratory failure (ARF) survivors was conducted. Panelists represented 14 countries (56% outside the United States). Results Seventy (92%) panelists completed the survey, including 32 researchers, 19 professional association representatives, 4 research funding representatives, and 15 ARF survivors/caregiver members. Among respondents, 91% reported that the time required to participate was appropriate and 96% were not bothered by reminders for timely response. Attributes of measurement instruments and voting results from previous rounds were evaluated differently across stakeholder groups. When measurement properties were explained in the stem of the survey question, 59 (84%) panelists (including 73% of survivors/families) correctly interpreted information about an instrument's reliability. Without a reminder in the stem, only 20 (29%) panelists (including 38% of researchers) correctly identified properties of a COS. Conclusion This international Delphi panel, including >20% patients/caregivers, favorably reported on feasibility of the methodology. Providing all panelists pertinent information/reminders about the project's objective at each voting round is important to informed decision making across all stakeholder groups.
- Published
- 2018
42. Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases
- Author
-
Samantha Harris, Brittany L. Adler, Clifton O. Bingham, Ana Maria Orbai, Ahmet Hoke, Homa Timlin, Lisa Christopher-Stine, Allan C. Gelber, Berna Aravidis, Jemima Albayda, Carlos A. Pardo, Brindusa Truta, Barney J. Stern, Pavan Bhargava, Edward K. Kasper, Kathryn C. Fitzgerald, Michelle Petri, Edward S. Chen, Christopher A. Mecoli, Mark Lazarev, Nisha A. Gilotra, Ami A. Shah, Ellen M. Mowry, Shiv Saidha, Scott D. Newsome, Julie J. Paik, Thomas E. Lloyd, Morgan Douglas, Alan N. Baer, Vinay Chaudhry, Eleni Tiniakou, Michelle Sharp, Elias S. Sotirchos, and Arun Venkatesan
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Disease ,Article ,Autoimmune Diseases ,03 medical and health sciences ,0302 clinical medicine ,COVID-19 Testing ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Pandemic ,Health care ,medicine ,Humans ,Pandemics ,030203 arthritis & rheumatology ,business.industry ,SARS-CoV-2 ,COVID-19 ,medicine.disease ,Mental health ,Comorbidity ,Infectious Diseases ,business ,030217 neurology & neurosurgery ,Kidney disease ,Social behavior - Abstract
Background People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. Methods We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. Results In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April–December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. Conclusions Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.
- Published
- 2021
43. RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES
- Author
-
Carlos A. Pardo, Samantha Harris, Brindusa Truta, Ami A. Shah, Ellen M. Mowry, Shiv Saidha, Kathryn C. Fitzgerald, Edward S. Chen, Julie J. Paik, Brittany L. Adler, Ana Maria Orbai, Barney J. Stern, Lisa Christopher-Stine, Allan C. Gelber, Homa Timlin, Jemima Albayda, Berna Aravidis, Arun Venkatesan, Elias S. Sotirchos, Eleni Tiniakou, Michelle Sharp, Thomas E. Lloyd, Scott D. Newsome, Morgan Douglas, Ahmet Hoke, Christopher A. Mecoli, Edward K. Kasper, Pavan Bhargava, Michelle Petri, Nisha A. Gilotra, Clifton O. Bingham, Vinay Chaudhry, Alan N. Baer, and Mark Lazarev
- Subjects
medicine.medical_specialty ,business.industry ,Disease ,medicine.disease ,Comorbidity ,Mental health ,Rheumatology ,AcademicSubjects/MED00290 ,Pulmonology ,Diabetes mellitus ,Internal medicine ,Health care ,Major Article ,medicine ,Intensive care medicine ,business ,Kidney disease - Abstract
BackgroundPeople with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences.ObjectiveAssess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care.DesignLongitudinal registry studyParticipants4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns HopkinsMeasurementsPeriodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcareResultsA total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption.LimitationsResults may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported.ConclusionsExposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.
- Published
- 2021
44. Immune checkpoint inhibitor-associated sarcoidosis: A usually benign disease that does not require immunotherapy discontinuation
- Author
-
Noémie Chanson, Manuel Ramos-Casals, Xerxes Pundole, Karijn Suijkerbuijk, Milton José de Barros e Silva, Merav Lidar, Karolina Benesova, Jan Leipe, Nihan Acar-Denizli, Pauline Pradère, Jean-Marie Michot, Anne- Laure Voisin, Maria E. Suárez-Almazor, Timothy R.D. Radstake, Virginia Fernandes Moça Trevisani, Hendrik Schulze-Koops, Audrey Melin, Caroline Robert, Xavier Mariette, Robert P. Baughman, Olivier Lambotte, Marie Kostine, Munther A. Khamashta, Leonard Calabrese, Maria Suárez-Almazor, Chiara Baldini, Clifton O. Bingham, Jacques-Eric Gottenberg, Thierry Schaeverbeke, Pilar Brito-Zerón, and Alejandra Flores-Chávez
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,Sarcoidosis ,medicine.medical_treatment ,Biopsy ,Ipilimumab ,Antibodies, Monoclonal, Humanized ,Young Adult ,Antineoplastic Agents, Immunological ,Internal medicine ,medicine ,Humans ,Adverse effect ,Immune Checkpoint Inhibitors ,Lung ,Melanoma ,Bilateral hilar lymphadenopathy ,Aged ,Aged, 80 and over ,business.industry ,Cancer ,Hydroxychloroquine ,Immunotherapy ,Middle Aged ,medicine.disease ,Discontinuation ,Nivolumab ,Oncology ,Female ,Lymph Nodes ,business ,medicine.drug - Abstract
Objective To analyse the clinical patterns of sarcoidosis triggered by immune checkpoint inhibitors (ICIs) in patients with cancer. Patients and methods The ImmunoCancer International Registry is a big data–sharing multidisciplinary network from 18 countries dedicated to evaluating the clinical research of immune-related adverse events related to cancer immunotherapies. Results We identified 32 patients with biopsy-proven sarcoidosis. Underlying cancer included mainly melanoma (n = 24). Cancer immunotherapy consisted of monotherapy in 19 cases (anti-PD-1 in 18 and ipilimumab in 1) or combined ipilimumab + nivolumab in 13. The time median interval between initiation of ICI and sarcoidosis diagnosis was 3 months (range, 2–29 months). The use of combined ICI was associated with a shorter delay in developing sarcoidosis symptoms. The disease was symptomatic in 19 (59%) cases with mostly cutaneous, respiratory and general symptoms. The organs involved included mainly the mediastinal lymph nodes (n = 32), the lungs (n = 11), the skin (n = 10) and the eyes (n = 5). Pulmonary computed tomography studies showed bilateral hilar lymphadenopathy in all cases. There was no severe manifestation. Specific systemic therapy was required in only 12 patients (37%): oral glucocorticoids in 9, and hydroxychloroquine in 3. ICIs were held in 25 patients (78%) and definitively discontinued in 18 (56%) patients. Seven patients continued ICI treatment with a second flare in one case. In six additional patients, an ICI was reintroduced with no harm, and sarcoidosis relapsed in one of them. Conclusion Our study shows that ICI-related sarcoidosis seems to have a specific profile, possibly more benign than that of idiopathic sarcoidosis, and does not necessarily imply ICI discontinuation.
- Published
- 2020
45. Spectrum and impact of checkpoint inhibitor-induced irAEs
- Author
-
Laura C, Cappelli and Clifton O, Bingham
- Subjects
Scleroderma, Systemic ,Myositis ,Sarcoidosis ,Arthritis ,Programmed Cell Death 1 Receptor ,Pharmacovigilance ,Sjogren's Syndrome ,Polymyalgia Rheumatica ,Neoplasms ,Rheumatic Diseases ,Humans ,CTLA-4 Antigen ,Mortality ,Immune Checkpoint Inhibitors - Published
- 2020
46. Identifying Minimal and Meaningful Change in a Patient-Reported Outcomes Measurement Information System for Rheumatoid Arthritis: Use of Multiple Methods and Perspectives
- Author
-
Anna Kristina Gutierrez, M. Jones, Kathleen M Andersen, Clifton O. Bingham, Uzma Haque, Ana Maria Orbai, Susan J. Bartlett, Vivian P. Bykerk, and Jeffrey R. Curtis
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pain Interference ,Pain ,Multiple methods ,Physical function ,Arthritis, Rheumatoid ,Short Forms ,Rheumatology ,medicine ,Humans ,Social determinants of health ,Patient Reported Outcome Measures ,skin and connective tissue diseases ,Fatigue ,business.industry ,medicine.disease ,Rheumatoid arthritis ,Cohort ,Physical therapy ,Observational study ,Female ,sense organs ,business ,Information Systems - Abstract
Rheumatoid arthritis (RA) is chronic, painful, disabling condition resulting in significant impairments in physical, emotional, and social health. Our objective was to use different methods and perspectives to evaluate the responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) short forms (SFs) and to identify minimal and meaningful score changes.Adults with RA who were enrolled in a multisite prospective observational cohort completed PROMIS physical function, pain interference, fatigue, and participation in social roles/activities SFs, the PROMIS 29-item form (PROMIS-29), and pain and patient global assessment, and rated change in specific symptoms and RA (a little versus lot better or worse) at the second visit. Physicians recorded joint counts, physician global assessment, and change in RA at visit 2. We compared mean score differences for minimal and meaningful improvement/worsening using patient and physician change ratings and distribution-based methods, and we visually inspected empirical cumulative distribution function curves by change categories.The 348 adults were mostly female (81%) with longstanding RA. Using patient ratings, generally 1-3-point differences were observed for minimal change and 3-7 points for meaningful change. Larger differences were observed with patient versus physician ratings and for symptom-specific versus RA change. Mean differences were similar among SF versions. Prespecified hypotheses about change in PROMIS physical function, pain interference, fatigue, and participation and legacy scales were supported.PROMIS SFs and the PROMIS-29 profiles are responsive to change and generally distinguish between minimal and meaningful improvement and worsening in key RA domains. These data add to a growing body of evidence demonstrating the robust psychometric properties of PROMIS and supporting its use in RA care, research, and decision-making.
- Published
- 2020
47. POS1459-HPR IDENTIFYING MEANINGFUL CHANGE IN THE RA FLARE QUESTIONNAIRE SCORES IN RHEUMATOID ARTHRITIS
- Author
-
Glen Hazlewood, Diane Tin, Marie-France Valois, Clifton O. Bingham, Louis Bessette, Carol A. Hitchon, E.C. Keystone, Janet E. Pope, Carter Thorne, Susan J. Bartlett, V.P. Bykerk, Gilles Boire, and Orit Schieir
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Swollen joints ,Disease ,Physical function ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Large cohort ,Disease activity ,Rheumatology ,Rheumatoid arthritis ,Early ra ,Physical therapy ,medicine ,Immunology and Allergy ,business - Abstract
Background:The RA-FQ is a patient-reported measure of current disease activity in RA that can be used to identify disease flares. The RA-FQ queries pain, physical function, fatigue, stiffness, and participation and yields a score from 0-50. We previously reported on reliability, validity, and responsiveness.Objectives:To identify changes in RA-FQ that represent minimal and meaningful improvement or worsening from the perspective of people with RA, treating rheumatologists, and in relation to disease activity indices. We hypothesized thatMethods:Data were from adults with early RA (sx Results:The 808 adults were mostly white (84%) women (71%) with a mean (SD) age of 55 (15) and moderate-high CDAI level (85%) at enrollment. Most (79%) reported their RA had changed; 59% were better and 20% worse. Patients who were a lot worse had a mean increase of 8.9 points whereas those who rated themselves as a lot better had a -6.0 decrease on the RA-FQ (Figure 1). Minimal worsening and improvement were associated with 4.7 and -1.8 change in RA-FQ scores, respectively, while patients who rated their RA unchanged had stable RA-FQ scores (Table 1).Similar changes were evident in CDAI, SDAI, and DAS indices (Table 1). Larger differences were observed with patient vs. physician global scores and tender vs. swollen joints. Across measures, the change associated with worsening was greater than for improvement. Results supported all prespecified hypotheses ab.Table 1.Spearman’s correlation coefficients of PsAQoL with the other parameters for construct validityDomainA Lot Better(N=346; 43%)A Little Better(N=132; 16%)The Same(N=174; 21%)A Little Worse(N=94; 12%)A Lot Worse(N=62; 8%)Δ95% CISDΔ95% CISDΔ95% CISDΔ95% CISDΔ95% CISDRA-FQ Total (0-50)-6.0(-7.1, -4.9)10.3-1.8(-3.2, -0.3)8.4-0.1(-1.3, 1.1)8.14.7(2.9, 6.6)9.18.9(5.1, 12.7)15.0 Pain-1.2(-1.4, -0.9)2.4-0.4(-0.8, 0.0)2.30.0(-0.2, 0.3)1.81.3(0.8, 1.7)2.22.0(1.2, 2.9)3.3 Physical Function-1.3(-1.6, -1.1)2.4-0.3(-0.6, 0.1)2.10.0(-0.3, 0.3)2.10.9(0.4, 1.4)2.41.8(0.8, 2.7)3.7 Fatigue-1.1(-1.4, -0.8)2.6-0.4(-0.7, 0.0)1.90.0(-0.3, 0.3)2.10.7(0.3, 1.1)2.11.3(0.5, 2.1)3.2 Stiffness-1.1(-1.4, -0.9)2.4-0.4(-0.7, 0.0)2.0-0.1(-0.4, 0.2)2.01.1(0.6, 1.5)2.21.8(1.0, 2.7)3.3 Participation-1.2(-1.5, -1.0)2.5-0.1(-0.5, 0.3)2.1-0.1(-0.4, 0.2)2.20.8(0.4, 1.3)2.22.0(1.1, 2.8)3.4Disease ActivityCDAI*-5.3(-6.3, -4.3)9.1-3.3(-5.4, -1.3)11.5-0.8(-2.0, 0.5)8.11.7(-0.1, 3.5)8.86.8(3.7, 9.8)12.0SDAI-5.6(-6.8, -4.4)9.2-3.5(-6.1, -0.9)12.2-1.9(-3.6, -0.2)8.91.5(-0.7, 3.7)9.24.7(1.0, 8.4)12.2DAS28-CRP-0.7(-0.8, -0.6)1.01-0.5(-0.7, -0.2)1.2-0.2(-0.4, 0.0)1.00.3(0.1, 0.5)1.00.5(0.2, 0.9)1.2Patient Global (0-10)-1.3(-1.5, -1.0)2.7-0.5(-0.9, -0.1)2.1-0.1(-0.4, 0.2)2.11.3(0.8, 1.8)2.42.9(2.1, 3.6)3.1MD Global (0-10)-1.2(-1.4, -1.0)1.9-0.7(-1.1, -0.3)-0.1-0.1(-0.4, 0.2)1.90.1(-0.3, 0.5)2.80.7(0.0, 1.5)2.8Swollen Joints (28)-1.4(-1.7, 1.0)3.2-1.0(-1.8, -0.2)4.6-0.4(-0.9, 0.0)3.00.0(-0.7, 0.7)3.41.3(0.2, 2.5)4.6Tender Joints (28)-1.5(-1.9, -1.1)3.9-1.3(-2.2, -0.3)5.50.0(-0.7, 0.6)4.30.3(-0.7, 1.2)4.52.2(0.8, 3.5)5.4Conclusion:In this large cohort of adults with ERA, the RA-FQ was responsive to change and generally distinguish between minimal and meaningful improvement and worsening. These data add to a growing evidence demonstrating robust psychometric properties of the RA-FQ and offer initial guidance about the amount of change associated with improvement or worsening, supporting its use in RA care, research and decision-making.Acknowledgements:The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation and Hoffmann-LaRoche since 2011; Medexus Inc. since 2013;, Merck Canada since 2017, Sandoz Canada, Biopharmaceuticals since 2019,Gilead Sciences Canada since 2020 and Fresenius Kabi Canada Ltd. since 2021. Previously funded by Janssen Biotech from 2011-2016, UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, Sanofi Genzyme from 2016-2017, and Eli Lilly Canada from 2016-2020.Disclosure of Interests:None declared
- Published
- 2021
48. Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications
- Author
-
Laura C. Cappelli and Clifton O. Bingham
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Myocarditis ,medicine.medical_treatment ,Inflammatory arthritis ,Immunology ,Article ,Polymyalgia rheumatica ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Neoplasms ,Rheumatic Diseases ,medicine ,Immunology and Allergy ,Humans ,Adverse effect ,Immune Checkpoint Inhibitors ,Myositis ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,Myasthenia gravis ,030220 oncology & carcinogenesis ,Plasmapheresis ,Immunotherapy ,Differential diagnosis ,business - Abstract
Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a range of musculoskeletal syndromes, such as crystalline arthritis, mechanical issues, and osteoarthritis, in addition to IRAEs. After diagnosing a rheumatic IRAE, rheumatologists must work with the patient and the oncologist to form a treatment plan. Treatment of IRAEs is guided by severity. Evidence for management is limited to observational studies. Inflammatory arthritis and polymyalgia rheumatica are treated with nonsteroidal antiinflammatory drugs in mild cases, glucocorticoids for moderate-to-severe cases, and sometimes require other disease-modifying antirheumatic drugs. Myositis due to ICIs can be accompanied by myocarditis or myasthenia gravis. Glucocorticoids and withholding the ICI are usually required to treat myositis; some patients with severe myositis require intravenous immunoglobulin or plasmapheresis. Further research is needed to optimize treatment of IRAEs that does not compromise the antitumor effect of ICIs.
- Published
- 2020
49. Postapproval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Antirheumatic Drugs: 5-Year Results from a United States-Based Rheumatoid Arthritis Registry
- Author
-
Heather J. Litman, Andrea Shapiro, Christine J. Barr, Clifton O. Bingham, Jeff Greenberg, Carol A. Connell, Arthur Kavanaugh, Dimitrios A. Pappas, Jamie Geier, Jose Luis Rivas, Alina Onofrei, Laura C. Cappelli, Joel M. Kremer, Kimberly J. Dandreo, and Ann Madsen
- Subjects
medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Tofacitinib ,business.industry ,Proportional hazards model ,Hazard ratio ,Original Articles ,medicine.disease ,Confidence interval ,Rheumatology ,Rheumatoid arthritis ,Internal medicine ,Medicine ,Original Article ,lcsh:RC925-935 ,business ,Adverse effect ,Mace ,Janus kinase inhibitor - Abstract
Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. Methods IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively. Results For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively. Conclusion In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.
- Published
- 2020
50. Having Patients and Providers Identify Meaningful Changes in Rheumatoid Arthritis Symptoms
- Author
-
Susan J. Bartlett and Clifton O. Bingham
- Subjects
medicine.medical_specialty ,business.industry ,Rheumatoid arthritis ,Internal medicine ,Medicine ,business ,medicine.disease - Published
- 2020
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.